Tau and amyloid imaging in presymptomatic and symptomatic Alzheimer’s disease with [F-18]THK5117 and [C-11]PiB: A multimodal imaging study

Tau and amyloid imaging now make it possible to image the spectrum of Alzheimer's Disease (AD) pathology in vivo. Both amyloid and tau pathology begin prior to symptom onset, but their spatial onset relative to one another is not known. This study examines regional distribution of amyloid and tau deposition during various stages of symptomatic disease and various stages of risk using [F-18]THK5117 and [C-11]PIB. A series of subjects from the Wisconsin Registry for Alzheimer's Prevention and Wisconsin Alzheimer's Disease Research Center who possessed varying levels of risk for AD and varying levels of cognitive decline were studied with T1-weighted MRI, [C-11]PIB and [F-18]THK-5117 positron emission tomography (PET) scans at the UW-Madison Waisman Center. MR scans were performed on a GE SIGNA 750, and PET scans on a Siemens ECAT HR+. PET images were motion corrected, denoised, and coregistered to MRI. Standard uptake value ratio (SUVR) maps were created by summing the last 30 minutes of a 90 and 70 minute dynamic scan for THK5117 and PIB respectively. The whole cerebellum was used as the reference region for both scans. Motion correction and coregistration to the T1-weighted volume were done with SPM12. Freesurfer derived standard cortical ROIs and manually derived custom ROIs were used to examine regional uptake. Examples shown include a patient with mild AD dementia, a cognitive decliner and a cognitively stable normal subject. Relative spatial deposition of tau and amyloid were compared. An AD patient exhibited strong tau (Braak stage VI) and amyloid binding, particularly in the lateral temporal lobes. A cognitive decliner who had been followed in the WRAP study for 10 years, though still not clinical MCI, exhibited tau binding in the perirhinal cortex (uncus) as well as hippocampus consistent with Braak Stage III and was also PiB positive. The stable normal subject, also followed for 10 years, was tau negative but strongly PIB positive. THK and PIB show different cortical binding patterns across a spectrum of AD severity. There was evidence for PIB binding at all levels of disease severity, while THK5117 binding was more apparent with cognitive decline in this preliminary series.